Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.

ERCP-directed radiofrequency ablation and photodynamic therapy are associated with comparable survival in the treatment of unresectable cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor 5-year survival rate (5%-10%). ERCP-directed radiofrequency ablation (RFA) or photodynamic therapy (PDT) can be performed as palliative therapy for unresectable CCA. ERCP with PDT is associated with improved survival compared with stent placement alone. However, ERCP-directed RFA has not been directly compared with PDT in patients with CCA. OBJECTIVE: To compare overall survival in patients with unresectable CCA who underwent palliative ERCP-directed RFA versus PDT. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Forty-eight patients with unresectable CCA who underwent ERCP-directed ablative therapy for palliation of unresectable CCA. INTERVENTIONS: ERCP-directed RFA or PDT. MAIN OUTCOME MEASUREMENTS: Overall survival by Kaplan-Meier analysis after initial treatment with either RFA or PDT. RESULTS: Patients who underwent RFA (n = 16) demonstrated an overall survival similar to that of those who underwent PDT (n = 32), with a median survival of 9.6 versus 7.5 months, respectively (P = .799). Patient age (P = .45), sex (P = .52), and lead time (P = .59) from presentation to initial RFA or PDT had no significant association with survival. The presence of distant metastasis was inversely associated with survival (hazard ratio 3.55; 95% confidence interval, 1.29-9.77; P = .014). Patients who underwent RFA (compared with PDT) had a lower mean number of plastic stents placed per month (0.45 vs 1.10, P = .001) but also had more episodes of stent occlusion (0.06 vs 0.02, P = .008) and cholangitis (0.13 vs 0.05, P = .008) per month. LIMITATIONS: Retrospective, single-center design. CONCLUSIONS: Survival after ERCP-directed RFA and PDT was not statistically different in patients with unresectable CCA. A randomized, controlled trial is warranted to validate these preliminary results.